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Cancer is seen as a complex disease that proceeds with numerous genetic changes, including oncogenes, tumor suppressors, DNA repair, cancer metabolism, and genetic origin, leading to excessive growth, metastasis, and drug resistance. Medicine knows various methods for cancer treatment and therapy, such as chemotherapy, interventional oncology, radiotherapy, surgery, hematological oncology, and others. In fact, some of the most promising methods are aimed at destroying tumor cells and deterring their metastasization.

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The modern era of cancer treatment is constantly evolving, with new breakthroughs and discoveries changing the course of treatment and therapy. It is these innovative approaches that we look at in today's article.

What-is-cancer

What is cancer

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Cells are the main units that make up the human body. They grow and divide to create new cells, as the body needs them. Usually, cells die when they become too old or damaged. Then new cells appear in their place.

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Cancer begins when genetic changes interfere with this consistent and rigorous process. Cells begin to grow uncontrollably and can form a mass called a "tumor". The tumor can be cancerous or benign. A cancerous tumor is a malignant formation, which means it can grow and spread to other parts of the body. A benign tumor means that the tumor can grow, but it will not spread.

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Generally speaking, cancer refers to cells that grow uncontrollably and invade other tissues. Cells can become cancerous due to the accumulation of defects or mutations in their DNA. Most of the time, cells are able to detect and repair DNA damage. If a cell is severely damaged and cannot recover, it usually undergoes so-called programmed cell death or apoptosis. Cancer occurs when damaged cells grow, divide and spread unusually, instead of self-destruct.

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As cancer develops in the body, it uses different mechanisms to progress and affect various organs and tissues. One of these mechanisms involves blood supply - large tumor formations rely on it to deliver oxygen and nutrients to help them grow. As tumors grow, these blood vessels are unable to provide oxygen and nutrients to any part of the tumor, leading to areas with decreased oxygen levels. However, this environment over time leads to the accumulation of acid in tumor cells.

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British-Columbia-researchers'-discovery

British Columbia researchers' discovery

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To cope with the stress that arises, cells adapt by releasing enzymes that neutralize the acidic conditions of their environment, allowing the cells not only to survive but also to become a more aggressive form of tumor, capable of spreading to other organs. One of these enzymes is called "carboanhydrase IX" (CAIX). A team of researchers from the Faculty of Medicine and the Institute of Cancer Research at the Тhe University of British Columbia discovered the anticancer effect of this enzyme and found that it inhibits cell growth. This is exactly what makes it the "Achilles heel" of cancer cells.

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In the same study, the research team looked at cell properties and identified the weaknesses of the enzyme "CAIX". They found that the enzyme works through a powerful mechanism known as the 'genome-wide synthetic lethal screen'. This tool looks at the genetics of a cancer cell and systematically erases one gene at a time to determine whether it can be destroyed by eliminating the CAIX enzyme along with another specific gene. [<a href="https://www.science.org/doi/10.1126/sciadv.abj0364" target="_blank" rel="noopener">ref.1</a>]

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According to Dr. Dedhar - a professor in the faculty and one of the authors of the study, this form of cell death occurs when iron accumulates and weakens the metabolism of the tumour and cell membranes. In June 2021 “Kojin Therapeutics” raised $60 million to accelerate research started at Harvard University and the Dana-Farber Cancer Institute, which involves the use of small molecules to destroy cells that are most vulnerable to ferroptosis. [<a href="https://www.fiercebiotech.com/biotech/kojin-bags-60m-to-exploit-weakness-drug-resistant-cancers" target="_blank" rel="noopener">ref.5</a>]

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Dr. Dedhar's research team has also found that combining CAIX inhibitors, including SLC-0111, with compounds known to cause ferroptosis, leads to catastrophic cell death and debilitates tumor growth. [<a href="https://www.science.org/doi/10.1126/sciadv.abj0364" target="_blank" rel="noopener">ref.1</a>][<a href="https://pubmed.ncbi.nlm.nih.gov/21606941/" target="_blank" rel="noopener">ref.3]</a>

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New-strategies-for-cancer-treatment---what-are-the-horizons

New strategies for cancer treatment - what are the horizons

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The results of the study, published August 27, 2021 in the multidisciplinary journal Science Advances, are expected to help researchers develop new cancer treatment strategies. [<a href="https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abj0364" target="_blank" rel="noopener">ref.2]</a> Their goal is to limit the progression of solid cancerous tumor formations, which represent the majority of tumor species occurring in the human body.

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Dr. Shoukat Dedhar said another unique compound known as "SLC-0111" had previously been identified. It is currently being investigated in phase 1 clinical trials (initial human testing) as a potent inhibitor of the CAIX enzyme. While preclinical models of breast, pancreatic, and brain cancer have shown the effectiveness of this compound in suppressing tumor growth and spread, other cellular properties reduce its effectiveness. Therefore, more research is needed to confirm its potential and dependence on other factors.

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In other studies on the topic, scientists looked at methods of targeting hypoxia in cancer therapy and destroying cancerous tumors. [<a href="https://pubmed.ncbi.nlm.nih.gov/21606941/" target="_blank" rel="noopener">ref.3</a>] The two main approaches to this are bioreductive&nbsp;(hypoxia-activated) prodrugs (modified drugs that are transformable before they become pharmacologically active) and inhibitors of molecules on which the survival of hypoxic cells depends.&nbsp;

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In short, this is a new type of programmed cell death and is closely related to both the maintenance of homeostasis and the development of diseases, especially cancers. [<a href="https://www.frontiersin.org/articles/10.3389/fonc.2020.571127/full" target="_blank" rel="noopener">ref.4</a>]

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It is worth mentioning another step in the progress of cancer treatment. A new drug that can stop tumour growth will be offered to National Health Service patients with lung cancer - the first in Europe to receive the drug. The drug is aimed at the mutation of the KRAS gene found in a quarter of all tumours, which has become known as the "Death Star" mutation due to its spherical appearance. National Health Service researchers have spent 40 years looking for the key to this mutation, and if the treatment works, it could represent a major breakthrough in the fight against other cancers, such as pancreatic cancer and colorectal cancer. [<a href="https://www.independent.co.uk/news/uk/home-news/lung-cancer-drug-tumour-nhs-b1917632.html" target="_blank" rel="noopener">ref.6</a>]

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We should remember that cancer belongs to the group of treatable diseases, and every step in the process of diagnosis and treatment is crucial for a favorable development. Our team will keep you up to date on the latest discoveries and achievements in the field, as always at <a href="../../" target="_blank" rel="noopener">&nbsp;Sanat.io.</a>

A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis

Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors, Science Advances 27 Aug 2021

Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011 Jun;11(6):393-410. doi: 10.1038/nrc3064. PMID: 21606941.

Ferroptosis in Cancer Treatment: Another Way to Rome Front. Oncol., 25 September 2020

Kojin bags $60M to exploit weakness of drug-resistant cancers

Lung cancer patients in England to receive 'breakthrough' tumour-stopping drug

There are 14,480 new cases of cervical cancer expected in the states in 2021, according to the American Cancer Society (1). Any woman can be affected by this disease. Fortunately, there are methods that can prevent the appearance of cervical cancer. One such method is the vaccine against human papilloma virus (HPV). 

How can the HPV vaccine protect us from cervical cancer?

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Over 50% of the population is infected with the gastric bacterium Helicobacter pylori. Although in many cases it remains asymptomatic, it often leads to diseases such as gastritis, ulcers and even stomach cancer. Conventional treatment is not always effective due to the growing resistance of the bacterium to existing antibiotics. This requires looking for alternatives and concomitant therapies and here we will look at what science says about 5 natural remedies in the fight against Helicobacter pylori.

Natural Treatments for Helicobacter pylori

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Marijuana is a plant with various effects on human health. Nowadays, its use for personal or medical purpose is becoming more prevalent. What is the story, are there enough studies to justify the positive and negative effects of marijuana use on health and what are these effects? The answers to these questions can be found in this article.

Marijuana – a peek into the history, the science of its active substances and their effects on health

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Silymarin has been used as a healing agent since ancient times. How its healing properties are manifested in the organism and what they are, you can find out in this article.

Silymarin - a well-known ancient herb - for the benefits in humans and animals

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There are various medical methods for the treatment and therapy of cancer, such as chemotherapy, interventional oncology, radiation therapy, surgery, hematological oncology, and others. One of the most promising methods is aimed at destroying tumor cells and preventing their metastasis.

A light at the end of the tunnel - cancerous tumors and their "Achilles heel"

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Snake venom is known as a method of treatment from antiquity, but only today science manages to unravel some of its secrets. In this article you will learn what snake venom contains, in which medications it is found and how it is used, as well as if it has any application in the treatment of cancer.

The Healing Properties Of Snake Venom - From Ancient Times To Modern Cancer Treatment

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What are the most famous natural sweeteners, what they are and from which plants are extracted. The answers to these questions can be found in the following article.

Sweetness From Nature Or How To Replace Sugar With Natural Sweeteners

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In this article, you will learn what health benefits spirulina consumption brings according to science, as well as tips for growing it at home.

5 Reasons Why Spirulina Truly Is A Superfood And How To Grow It Home

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Cancer is a treacherous and severe disease that is detrimental not only to the body but also to the human spirit. When it is malignant (in very rare cases benign tumors are also life-threatening), it can mean years of struggle and survival attempts. New immunological cancer therapies offer hope for a better outcome, years of survival, and successful recovery therapy.

 A light at the end of the tunnel - cancerous tumors and their

Бетина Цветкова

Most common causes of recurrent pregnancy loss

Many women's dream is to start a family, to watch how one, two, three or even more little people grow up before their eyes and become big girls and boys, full of dreams and a desire for adventure. Unfortunately, however, not everyone is favoured with this opportunity. About 2-2.5% of women undergo two or more miscarriages, which is defined as recurrent pregnancy loss (RPL) and may be associated with reproductive problems (1).

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In this article, we will discuss the most common causes, as well as other main factors that are believed to contribute to repeated miscarriages. Finally, we will talk about what type of tests can be done to establish the cause and what treatments and methods are applied to overcome this problem.

Most-common-causes-of-recurrent-abortions

Most common causes of recurrent abortions

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There are many reasons that are considered leading in repeated pregnancy loss. As science and medicine progress, the influence of more and more factors is proven, which sometimes creates differences in conclusions between different state reproductive organizations. As leading factors, genetic, anatomical, endocrinological and immunological problems are noted.

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Anatomical-factors

Anatomical factors

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Anatomical defects in the uterus occur in 10%-15% of cases of repeated abortions (6). It is believed that the way they contribute to a miscarriage is by cutting blood circulation to the lining of the uterus (endometrium), which in turn leads to a number of reproductive problems. The most common anatomical defects found in women undergoing RPL are congenital genetic defects, intrauterine adhesions and uterine fibroids or polyps (6).

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Intrauterus adhesions, often associated with Asherman's syndrome, are common in RPL. They can be developed after a coarse curettage or other surgical interventions of the uterus, birth by caesarean section, radiotherapy, endometriosis or various infections such as genital tuberculosis. Adhesions of the uterus are caused by the formation of a cicatricial connective tissue resembling scars of the endometrium and leads to a change in its size and shape. Depending on the size of conglutination, this condition may not constitute a problem or even lead to infertility (7).

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Uterine fibroids and polyps are also associated with recurrent pregnancy loss. Fibroids, also called myomas or leiomyomas, are harmless growths from the muscle tissue of the uterus, while polyps are growths from the endometrium. Many women have such excrescences but most do not pose a problem. These formations can lead to miscarriage by preventing the egg from being properly implanted into the uterus. According to the American Society for Reproductive Medicine, 5%-10% of sterile women have myomas (8).

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Genetic-factors

Genetic factors

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Genetic factors include mainly chromosomal abnormalities, which can usually occur with the development of the embryo or be inherited from the parents. It is believed that about 2%-8% of couples who suffer from repeated pregnancy loss have an abnormal karyotype (karyotype is the totality of all chromosomes) (2), but embryonic chromosomal abnormalities are rare in RPL (4). About 50%-60% of all early miscarriages are due to defects in the karyotype (2). The most common hereditary chromosomal abnormalities in recurrent pregnancy loss are translocations, with the most commonly observed in RPL being reciprocal (about 60% of the translocations) and Robertson translocations (about 40% of the translocations).

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Genetic-factors_0_2

Reciprocal translocation is called the exchange of genetic material between two different chromosomes, and Robertson translocation is the joining of the long arms of one chromosome with the long arms of another chromosome and of the short ones with the short ones, forming two wrong-sized chromosomes (4). Although we have no influence on these genetic events, most parents who carry such genetic defects give life to a perfectly healthy child. If you have already suffered a miscarriage caused by chromosomal abnormalities, the probability of a subsequent abortion for the same reason is very low.

Endocrinological-factors

Endocrinological factors

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17%-20% of recurrent pregnancy loss is associated with endocrinological problems in women. The main ones are polycystic ovary syndrome, diabetes mellitus, thyroid disease. Scientists are discussing the possibility that a defect in the luteal phase of the menstrual cycle may have an impact on RPL, but this is still up for debate. Polycystic ovary syndrome is found in at least 40% of women who go through repeated pregnancy loss (9).

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These women are known to have insulin resistance and hyperinsolemia, hyperandrogemia and increased levels of a plasminogen activator-1 inhibitor – factors that have been proven to interfere with the course of normal pregnancy (6,10). In women suffering from diabetes mellitus, there is no increased risk of miscarriage, as long as insulin and glycosylated haemoglobin levels are kept to normal (11). &nbsp;Similarly, women with hypothyroidism may have a normal pregnancy and a healthy child if maintaining normal levels of thyroid hormone. If levels are not regulated during pregnancy, the risk of abortion, as well as of congenital genetic problems of the child after birth increase (12).

Immunological-factors

Immunological factors

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With the development of science there is deeper understanding of the influence of immunological factors on RPL. During implantation of the egg in the uterus, in the formation of the placenta and in the development of the embryo, a large number of different immune processes are involved, immune teams of guards, the role of which is to accompany and preserve the normal course of all these reproductive processes.

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Unfortunately, however, in some cases, the immune cells – guards make mistakes and cause problems in pregnancy. A main such problem is antiphospholipid antibody syndrome, which occurs in 15% of patients who undergo recurrent abortions (13). This is a rare autoimmune disease in which the immune system mistakenly attacks parts of the cell membrane called phospholipids. The cells that make up the lining of blood vessels are damaged, which causes increased formation of clots in the blood. This is a major problem in pregnant women, because communication between the mother and the embryo happens by blood. This disease can lead to blockage of blood vessels in the placenta, which would interfere with the development of the embryo and therefore lead to miscarriage. Another immunological factor for RPL is considered the possibility of the mother organism not recognizing the fetus as its own and disposing of it. Since the embryo carries genetic information from both the mother and the father, the paternal antigens which the fetus presents may be identified as alien by the mother's immune system and the placenta may be discarded (14).

Other-factors-associated-with-THE-PA

Other factors associated with THE PA

Thrombophilia

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The main thrombophilia most often associated with repeated pregnancy loss are:

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(a) Hyperhomocysteinemia, which occurs from a mutation in a specific gene called methylenetetrahydrofolate reductase (MTHFR). Opinions in science are still conflicting about whether this gene has any connection to vascular diseases at all, but many of the women who undergo repeated abortions have this mutation.

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b) Resistance to activated protein C – occurs from a mutation in Factor V Leiden. This mutation is a major genetic change in thrombophilia, since with its presence it is considered that the body goes into a state of hypercoagulation.

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c) Deficiency of activated protein C and protein S – these can be both congenital and acquired as a result of liver diseases, some infections, vitamin K deficiency and others. Congenital protein C deficiency arises from a mutation in the PROC gene, and in protein S - from a mutation in the PROS1 gene.

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(d) Mutations in prothrombin and antithrombin.

Fragmentation-of-sperm-DNA

Fragmentation of sperm DNA

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In a large number of cases of repeated abortions the cause is not in the woman but in the other partner, whose genetic material is also transmitted to the fetus. Most men have a subpopulation of sperm in their ejaculate, the DNA of which is damaged before or during ejaculation. In some subfertile men, the number of such spermatozoa is increased and this may be associated with the advent of repeated miscarriages (18).

Impact-of-environmental-factors-on-the-occurrence-of-recurrent-miscarriages

Impact of environmental factors on the occurrence of recurrent miscarriages

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There are various factors which some people face every day, which may contribute to the risk of recurrent miscarriages. Daily alcohol, cigarettes and coffee intake are most commonly discussed. Drinking alcohol 3 times a week for the first 3 months or 5 times a week during pregnancy has been shown to increase the risk of miscarriages. Smoking cigarettes is associated with constriction of blood vessels due to the presence of nicotine in them, which reduces blood circulation to the placenta and can be the cause of miscarriage (6). Coffee intake can also be a factor in miscarriage, as has been demonstrated in some studies (16,17). Although there are clearly risks of taking these substances, no link has yet been found between their intake and RPL.

What-tests-can-you-do-to-find-the-cause?

What tests can you do to find the cause?

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A visit to the gynecologist is inevitable after a miscarriage. While you are in the office, hysteroscopy can be done – a study in which the doctor examines the condition of the uterus from the inside using a small camera. Another study that is done in a specific place for the procedure is a hysterosalpingogram. In this study, fluoroscopy is performed – a contrast agent is injected into the cervix, which diffuses along the uterus and fallopian tubes. The process is observed on an X-ray and it visualizes whether there is a blockage of the fallopian tubes.

What-tests-can-you-do-to-find-the-cause?_2_1

Conducting cytogenetic analysis is a commonly prescribed study in patients who have suffered repeated miscarriages. Cytogenetic analysis allows to see all the chromosomes of the patient after only one blood collection. Chromosomes are isolated from the blood cells and then stained by a special method, allowing them to be seen under a microscope and to find out if any chromosomal defects are present.

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What-tests-can-you-do-to-find-the-cause?_2_3

Examination of hormones such as thyroid stimulating hormone (TSH), checking the ovarian reserve by examining follicle-stimulating hormone (FSH) and estradiol may be useful in RPL. If you experience irregular menstruation, it can be seen whether antithyroid antibodies are present, which are detected in 17%-33% of women who have suffered 3 or more miscarriages (19). Checking if insulin resistance is present may also be helpful after undergoing RPL.

What-tests-can-you-do-to-find-the-cause?_2_4

Since antiphospholipid syndrome is indisputably associated with repeated abortions, it is significant to test for the presence of anticardiolipin antibodies and lupus anticoagulant, which will indicate whether the patient has an increased risk of forming blood clots.

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What-tests-can-you-do-to-find-the-cause?_2_6

Despite numerous associations of thrombophilia with miscarriages in women, they have not yet been accepted as a major factor in repeated abortions, but rather as an accompanying factor to other factors that make a greater contribution to the occurrence of such events. Nevertheless, it is advisable that women who have a history of thrombosis take a blood test for the presence of thrombophilia.

What-tests-can-you-do-to-find-the-cause?_2_7

Last but not least, it is important to establish whether the cause of RPL comes from the male partner by examining the seminal fluid for DNA fragmentation. There are several different methods that can be conducted for this analysis, but all of them evaluate whether there is damage in sperm DNA.

What-tests-can-you-do-to-find-the-cause?_2_8

Therapies-that-may-improve-the-chances-of-conception-in-RPL

Therapies that may improve the chances of conception in RPL

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If an anatomical problem is detected, it can be removed surgically which often gives good results. If there are genetic abnormalities, including fragmentation of DNA in spermatozoa, the best option is to approach various in vitro procedures. Therapy with insulin-sensitive agents such as metformin improves performance in women with polycystic ovary syndrome (20). If there is an increased risk of thrombus formation, therapy with low molecular weight anticoagulants, such as heparin, is recommended. For some women, it is even advisable to continue taking them during pregnancy. Other easy changes that can be done in everyday life that can have big impact on the improvement in the chances of conception is the management of a healthy lifestyle by both partners – healthy eating, more movement, no drinking of alcohol, coffee and no smoking cigarettes, taking vitamins and antioxidants.

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Conclusion

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Nowadays, about 25%-30% of women go through hardships to discover the cause of repeated abortions, many of which even remain unclear. It is believed that in about 40%-50% of cases the exact cause cannot be found (6). However, most women who undergo repeated miscarriages (about 70%-75% of them) subsequently manage to give life to a healthy child (3).

Conclusion_4_1

Dimitriadis, E., Menkhorst, E., Saito, S.&nbsp;et al. (2020).&nbsp;Recurrent pregnancy loss.&nbsp;Nature Reviews Disease Primers6, <a href="https://doi.org/10.1038/s41572-020-00228-z" target="_blank" rel="noopener">https://doi.org/10.1038/s41572-020-00228-z</a>

Pal, A. K., et al. (2018). Chromosomal Aberrations in Couples with Pregnancy Loss: A Retrospective Study.&nbsp;Journal of human reproductive sciences, 11(3), 247–253. <a href="https://doi.org/10.4103/jhrs.JHRS_124_17" target="_blank" rel="noopener">https://doi.org/10.4103/jhrs.JHRS_124_17</a>

Hyde, K. J., &amp; Schust, D. J. (2015). Genetic considerations in recurrent pregnancy loss.&nbsp;Cold Spring Harbor perspectives in medicine, 5(3), a023119. <a href="https://doi.org/10.1101/cshperspect.a023119" target="_blank" rel="noopener">https://doi.org/10.1101/cshperspect.a023119</a>

El Hachem, H., et al. (2017). Recurrent pregnancy loss: current perspectives.&nbsp;International journal of women's health, 9, 331–345. <a href="https://doi.org/10.2147/IJWH.S100817" target="_blank" rel="noopener">https://doi.org/10.2147/IJWH.S100817</a>

Danielsson, K. (2020). How a septate uterus increases miscarriage risk. VeryWellFamily

Ford, H.B., &amp; Schust, D. J. (2009). Recurrent pregnancy loss: etiology, diagnosis, and therapy.&nbsp;Reviews in obstetrics &amp; gynecology, 2(2), 76–83.

Asherman syndrome - adhesions in the uterine cavity - en

Care England. Uterine Fibroids, Polyps &amp; Abnormalities. womenandinfants.org

Raj, Raj, Backos, M., Rushworth, F., Regan, L. (2000). Polycystic ovaries and recurrent miscarriage—a reappraisal, Human Reproduction, Volume 15, Issue 3, Pages 612–615, <a href="https://doi.org/10.1093/humrep/15.3.612" target="_blank" rel="noopener">https://doi.org/10.1093/humrep/15.3.612</a><a href="https://pubmed.ncbi.nlm.nih.gov/14669168/" target="_blank" rel="noopener">https://pubmed.ncbi.nlm.nih.gov/14669168/</a>

Mills, J. L. et al. (1988). Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identifies within 21 days of conception. The New England Journal of Medicine. 319:1617-1623. DOI: 10.1056/NEJM198812223192501

Thyroid Disorders and Pregnancy | Children's Hospital of Philadelphia

Di Prima, F. A. et al. (2011). Antiphospholipid Syndrome during pregnancy: the state of the art. Journal of prenatal medicine, 5(2), 41–53.

W. Tang, Z. Alfirevic, S. Quenby, Natural killer cells and pregnancy outcomes in women with recurrent miscarriage and infertility: a systematic review, Human Reproduction, Volume 26, Issue 8, August 2011, Pages 1971–1980, <a href="https://doi.org/10.1093/humrep/der164" target="_blank" rel="noopener">https://doi.org/10.1093/humrep/der164</a>

Kwak, J.Y., Beer, A.E., Kim, S.H. and Mantouvalos, H.P. (1999), Immunopathology of the Implantation Site Utilizing Monoclonal Antibodies to Natural Killer Cells in Women with Recurrent Pregnancy Losses. American Journal of Reproductive Immunology, 41: 91-98.&nbsp;<a href="https://doi.org/10.1111/j.1600-0897.1999.tb00080.x" target="_blank" rel="noopener">https://doi.org/10.1111/j.1600-0897.1999.tb00080.x</a>

Rasch, V. (2003), Cigarette, alcohol, and caffeine consumption: risk factors for spontaneous abortion. Acta Obstetricia et Gynecologica Scandinavica, 82: 182-188.&nbsp;<a href="https://doi.org/10.1034/j.1600-0412.2003.00078.x" target="_blank" rel="noopener">https://doi.org/10.1034/j.1600-0412.2003.00078.x</a>

Cnattingius, et al. (2000). Caffeine Intake and the Risk of First-Trimester Spontaneous Abortion. New England Journal of Medicine. 343.25. Pages 1839-1845. DOI: 10.1056/NEJM200012213432503

Robinson, L., et al. (2012). The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis, Human Reproduction, Volume 27, Issue 10, Pages 2908–2917, <a href="https://doi.org/10.1093/humrep/des261" target="_blank" rel="noopener">https://doi.org/10.1093/humrep/des261</a>

Antithyroid antibodies TATE MAT. Reproinova.com

Feng, Ye &amp; Yang, H. (2017) Metformin – a potentially effective drug for gestational diabetes mellitus: a systematic review and meta-analysis, The Journal of Maternal-Fetal &amp; Neonatal Medicine,&nbsp;30:15,&nbsp;1874-1881,&nbsp;DOI: <a href="https://doi.org/10.1080/14767058.2016.1228061" target="_blank" rel="noopener">10.1080/14767058.2016.1228061</a>

Most common causes of recurrent pregnancy loss

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 Most common causes of recurrent pregnancy loss

Ивелина Янкова

Author: Sylvia Marinova, PhD student in in the "Genomic Stability" lab at BAS

Gin tonic - a favorite drink, which we can safely call one of the symbols of warm summer evenings, filled with broad smiles and high spirits in the presence of good company. And this is only the simplest variation of this refreshing drink - with a little imagination one could add wonderful notes of variety and taste, and at the end of the article you will find a few original ideas for easy cocktails with gin. Until then - let's turn to the curious and less familiar facts about the history and benefits of gin.

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Where does gin come from

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As a national drink of the British, you might easily think that the gin originated from there. But that's not quite the case. It turns out that the drink has a longer history.

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Francisco Sylvius, physician from the Leiden University, is officially thought to be the discoverer of&nbsp; gin. He was first to describe the production of the drink in the 17th century by distilling fermented cereals, namely malt wine, to which "fruit" of juniper was added during the process.&nbsp; It has strong aromatic and healing properties, and the resulting drink he used as a medicine mainly for kidney problems. He called the juniper liqueur - gin (in Latin juniper is Juniperus).

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Although his name is traditionally mentioned as the discoverer of gin, there is various evidence to suggest that even previously, high-alcohol distilled juniper beverages were well known as a medicinal product [<a href="https://www.diffordsguide.com/g/1108/gin/history-of-gin-1100s-mid-1500s" target="_blank" rel="noopener">ref.1</a>]. For example, during the Black Death, the devastating bubonic plague epidemic that spread across Europe in the mid-14th century, there was a belief that distilled juniper drinks helped fight the disease. For this reason, they were very popular.

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Still, how does gin as we know it get to the British and to us? Even before Francisco Sylvius was born, the Dutch had produced large quantities of giniver and traded with it. In the 17th century, during the wars, English soldiers in the low lands called the giniver "Dutch courage". They shortened the name of the drink to gin and brought the new taste to their homeland. Then the gin industry flourished and the famous London gin was born.

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What about tonic water?

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It is also worth mentioning briefly about the history of tonic - after all, it is half of the drink gin tonic, and its origin is also associated with its healing properties.

Healing properties